Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia

Journal of Theoretical Biology
Morgan CraigMichael C Mackey

Abstract

The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed ...Continue Reading

References

Sep 1, 1976·The Journal of Clinical Investigation·J T DanceyC A Finch
Mar 9, 2000·Journal of Pharmaceutical Sciences·C J Porter, S A Charman
Jul 13, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E JohnstonG Schwab
May 12, 2001·Cell Proliferation·M C MacKey
Oct 27, 2001·Journal of Pharmacokinetics and Pharmacodynamics·B WangL K Roskos
Jul 10, 2003·Journal of Theoretical Biology·Samuel BernardMichael C Mackey
Jul 30, 2003·Clinical Pharmacokinetics·Ivan Nestorov
Aug 2, 2003·Investigational New Drugs·Lena E Friberg, Mats O Karlsson
Dec 8, 2004·The Journal of Pharmacology and Experimental Therapeutics·Danielle N McLennanSusan A Charman
Jun 25, 2005·Journal of Theoretical Biology·Caroline Colijn, Michael C Mackey
Aug 24, 2005·Journal of Theoretical Biology·Catherine FoleyMichael C Mackey
Jun 8, 2007·Bulletin of Mathematical Biology·E ShochatL A Segel
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eliezer Shochat, Vered Rom-Kedar
Nov 15, 2008·Journal of Theoretical Biology·Catherine Foley, Michael C Mackey
Jan 9, 2009·Immunology·Rebecca C Furze, Sara M Rankin
May 21, 2010·Journal of Leukocyte Biology·Sara M Rankin
Oct 15, 2010·Journal of Clinical Pharmacology·Wojciech KrzyzanskiSigrid Balser
Nov 26, 2010·Journal of Theoretical Biology·Jinzhi Lei, Michael C Mackey
May 19, 2011·Cancer Chemotherapy and Pharmacology·Carlos Pérez-RuixoJuan José Pérez-Ruixo
Nov 1, 2011·Journal of Theoretical Biology·Changjing ZhugeMichael C Mackey
Mar 14, 2012·PLoS Computational Biology·Sang Ok SongGilles Clermont
Aug 1, 2012·Theoretical Biology & Medical Modelling·Markus ScholzMarkus Loeffler
Sep 13, 2012·PLoS Computational Biology·Sang Ok SongGilles Clermont
Sep 18, 2012·Journal of Theoretical Biology·Grace BrooksMichael C Mackey
Oct 12, 2012·Clinical Pharmacokinetics·Mario González-SalesJuan Jose Pérez-Ruixo
Jun 26, 2014·CPT: Pharmacometrics & Systems Pharmacology·T A Leil

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Citations

Feb 14, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Xiaotian WuFahima Nekka
Jul 14, 2016·Journal of Pharmacokinetics and Pharmacodynamics·Xiaotian WuJun Li
Apr 1, 2018·Clinical Pharmacology and Therapeutics·Chiara FornariTeresa A Collins
Feb 6, 2018·Journal of Pharmacokinetics and Pharmacodynamics·Neil D EvansJames W T Yates
Apr 19, 2017·CPT: Pharmacometrics & Systems Pharmacology·M Craig
Nov 6, 2017·Journal of Cancer Research and Clinical Oncology·Sibylle SchirmMarkus Scholz
Jan 15, 2019·Journal of Mathematical Biology·Daniel C De Souza, Michael C Mackey
Jun 14, 2020·British Journal of Clinical Pharmacology·Michael C MackeyMorgan Craig
Aug 2, 2020·Bulletin of Mathematical Biology·Tyler CassidyMichael C Mackey

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